Argolyn Bioscience Inc. is an early stage biotechnology company that creates novel peptide drugs and diagnostics with greatly improved intrinsic pharmaceutical properties through substitution of non-natural amino acid analogues for arginine (Arg) or lysine (Lys). In proof-of concept studies thus far, application of the Argolyn technology to peptides of therapeutic interest has resulted in dramatic increases in receptor binding, induction of receptor selectivity, blood and plasma stabilization, and delivery through the blood brain barrier (BBB). A key question for our technology is its breadth: can any peptide of biological interest be improved? The Company currently has late-discovery-stage lead candidates in psychosis, pain, and thrombosis; the psychosis and thrombosis leads are being pursued through other STTRs (submitted) and currently active grants. In this proposal, we will use ABS17, our lead candidate in pain, as another vehicle with which to evaluate the robustness of the technology. We propose to evaluate the systemic pharmacokinetics, blood brain barrier access, oral bioavailability, microsomal stability, and preliminary toxicity of ABS17. Completion of the Specific Aims of this proposal, in combination with data already accumulated on this peptide, will "round out" the preclinical work and provide a third peptide candidate on which the Argolyn platform was successfully applied. It will also lead directly into the Phase 2 STTR that will address the technology more generically (immunogenicity, toxicity of the individual non-natural amino acid residues, and model peptides containing them, etc.).